Apoptosis is a complex process that plays a central role in physiological and pathological cell death. This fast evolving research area has experienced incredible development in the past few years. Progress in the knowledge of the structure of many of the main molecular actors of the apoptotic signal transduction pathways has driven the design of synthetic peptides that in some cases can function as simplified versions of their parent proteins. These molecules are contributing to a better understanding of the activity and regulation of apoptotic proteins and also are setting the basis for the discovery of effective drugs to combat important diseases related to apoptosis. Most applications of peptides in apoptosis research are so far related to caspases, caspase regulatory proteins, such as LAPs and Smac, and proteins of the Bcl-2 family. Additionally, important perspectives are open to other systems, such as the macromolecular assemblies that are responsible for the activation of initiator caspases.